Cycloalkyldiarylphosphines constitute a group of chemical products of considerable usefulness as ligands for making noble metal catalysts. Menthyldiphenylphosphine and neomenthyldiphenylphosphine are examples of ligands which impart to transition metal complexes the potential for diastereomeric interactions with unsaturated organic substrates, thus making asymmetric synthesis possible. Note in this connection, J. D. Morrison and W. F. Masler, J. Org. Chem., 1974, Vol. 39, No. 2, pages 270-272. Neomenthyldiphenylphosphine is of particular importance for the preparation of noble metal catalysts useful in the synthesis of certain pharmaceuticals such as naproxen, ketoprofen, ibuprofen, etc.
A known method of generating tertiary phosphines with two aryl groups and a dissimilar third hydrocarbyl group involves coupling a lithium diaryl phosphide with a halohydrocarbon such as benzyl chloride in an ether such as tetrahydrofuran. See A. M. Aguiar, J. Beisler and A. Mills, J. Org. Chem., 1962, Vol. 27, pages 1001-1005. Because the reaction co-produces a reactive aryl lithium coproduct which can complicate synthesis procedures, the authors (Aguiar et al.) developed a method of selectively eliminating this coproduct. They accomplished this by adding to the reaction mass an equivalent amount of tert-butyl chloride to selectively react with the aryl lithium so that isobutylene, aromatic. hydrocarbon and lithium chloride are formed. Nevertheless an extra reactant and a concurrent reaction were involved in this approach.
Another complicating factor in the reaction of lithium diaryl phosphide with a halohydrocarbon in tetrahydrofuran is that one or more components in the system tend to interact with the tetrahydrofuran whereby side reactions such as ring cleavage can occur under the conditions used. In addition, the reaction between lithium diaryl phosphide and menthyl chloride is slow and requires prolonged reaction periods, which in turn favors the opportunity for more adverse interaction with the cyclic ether solvent such as ring cleavage to occur.